Timothy J. Fries

Chronic inflammatory demyelinating polyradiculoneuropathy in diabetic patients.

This retrospective analysis was undertaken to determine whether a subset of diabetic patients with demyelinating polyneuropathy were similar to patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Ten patients meeting the clinical criteria for idiopathic CIDP were compared to nine patients with diabetes and demyelinating polyneuropathy. The diabetic patients with demyelinating polyneuropathy displayed clinical, electrophysiologic, and histologic features that were similar to those in CIDP patients. All six patients with diabetes and demyelinating polyneuropathy who were treated with immunomodulatory therapy showed a favorable response. Our study highlights the importance of investigating diabetic patients with polyneuropathy in an attempt to identify patients with demyelinating polyneuropathy, because of the likelihood of benefit in these patients from immunomodulatory treatment. Muscle Nerve 27: 465–470, 2003

A controlled trial of amino acid therapy in amyotrophic lateral sclerosis I. Clinical, functional, and maximum isometric torque data

We conducted a two center, double-blind, placebo-controlled treatment trial with oral branched chain amino acids (BCAA) (L-leucine 12 g, L-isoleucine 8 g, and L-valine 6.4 g daily) or L-threonine (4 g daily) with pyridoxal phosphate (160 mg daily) for six months in patients with amyotrophic lateral sclerosis (ALS). The effect of treatment on disease progression was estimated every two months by recording clinical muscle strength, maximum isometric muscle torque in selected muscles, forced vital capacity (FVC), activities of daily living pertaining to the upper and lower limbs, and timed tasks. Ninety-five patients were randomized to receive BCAA (n = 31), L-threonine (n = 32), or placebo (n = 32), of whom 77 (81%) completed the trial. Mean weight loss in the placebo group was 1.1 kg and in the L-threonine group was 3.2 kg; the BCAA group gained 0.2 kg (p = 0.04). The estimated decline in FVC was about 2.5 times greater in the BCAA and L-threonine groups as compared to placebo (p = 0.03). Otherwise, no significant differences were found in the changes observed in clinical, functional, timed, or maximum torque measures among treatment groups. The amino acids were well tolerated. The results of our study failed to show a beneficial effect of BCAA or L-threonine treatment for six months on the disease course in ALS. The higher rate of loss of pulmonary function in patients treated with BCAA or L-threonine may have been due to chance, but an adverse effect of these amino acids cannot be ruled out. NEUROLOGY 1996;47: 1220-1226

Topical Capsaicin in Painful Diabetic Neuropathy: Effect on Sensory Function

Objective –To examine the effect of capsaicin on sensory function in painful diabetic neuropathy. Research Design and Methods –We examined the effects of topical 0.075% capsaicin cream on thermal and vibration thresholds in 22 subjects with painful diabetic neuropathy who participated in a double-blind vehicle-controlled therapeutic trial. Results –After 8 wk of use, there was no significant change in warm and vibration thresholds, but the cold threshold was significantly reduced by capsaicin and vehicle creams to an equal degree. In fewer subjects who used capsaicin cream in an open-label study, there was no significant effect on sensory thresholds after up to 32 wk of use. Conclusions –Although our results and those of others show no adverse effects of topical 0.075% capsaicin on human sensory function, even in subjects with preexisting neuropathic sensory impairment, the small number of subjects tested does not justify an inferential statement on safety. Further studies in more subjects are warranted to ensure the long-term safety of capsaicin for pain relief in humans.

The effects of long-term non-fatiguing resistance exercise in subjects with post-polio syndrome

Measures of torque were used to evaluate changes in muscle strength and endurance in 17 patients with post-polio syndrome who did prescribed resistance exercise for up to 2 years. Exercise compliance averaged 75%, with 16 subjects increasing the weight lifted in training. Maximum torque was significantly increased in the exercised muscle compared to the control muscle; no difference was seen in muscle endurance. Individuals with post-polio syndrome can increase muscle strength by doing non-fatiguing resistance exercise, but they should undergo quantitative testing of muscle strength a minimum of every 3 months to guard against overwork weakness.

Focal neuropathy preceding chronic inflammatory demyelinating polyradiculoneuropathy by several years

We report three patients who exhibited an unusual clinical course of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in which mononeuropathic limb weakness developed 2,11 and 23 years, respectively, before the development of generalized polyradiculoneuropathy. The eventual diagnosis remained uncertain until other causes of neuropathy were excluded, and the clinical disorder progressed to involve the other limbs. Focal or regional variants of CIDP suggest that the pathologic, and perhaps the immunologic, abnormalities can be localized and selective for prolonged periods of time. Although this clinical variant seems to account for a small number of CIDP cases, its recognition may aid in making an early diagnosis.

Lurnbosacral radiculoplexopathy as a manifestation of Epstein‐Barr virus infection

We report the clinical features of five patients with lumbosacral radiculoplexopathy (LSRP) and one patient with a femoral neuropathy, all of whom had serologic evidence of a recent Epstein-Barr virus (EBV) infection. After a thorough investigation, no other etiology was apparent. Pain was a prominent feature in all cases, and the prognosis was generally good, with recovery in weeks to months. We conclude that LSRP may occur as a postinfectious process following recent EBV infection.

Double‐blind controlled trials of Cronassial in chronic neuromuscular diseases and ataxia

We report three 12-month, double-blind, three-phase studies comparing the effect of placebo and 40 mg and 100 mg IM daily of purified bovine brain gangliosides (Cronassial) in chronic neuromuscular diseases. Thirty patients with Charcot-Marie-Tooth disease, 16 with idiopathic polyneuropathy, and 30 with spinocerebellar degeneration had neuromuscular function measured monthly by quantitative testing of motor and sensory function, coordination, and electrophysiologic factors. Analysis of these studies, and of longer term (up to 2 years) open studies of 100 mg daily of Cronassial in 67 patients failed to show therapeutic efficacy of Cronassial. Statistical power calculations indicated that five of the 37 measures had greater than a 70% chance of detecting a 20% difference in the rate of progression of the active-drug and placebo groups. A number of measures significantly improved during prolonged placebo treatment, suggesting that the placebo effect has a strong influence on “objective” measures of neuromuscular function.

Metastasizing thymoma and myasthenia gravis. Favorable response to glucocorticoids after failed chemotherapy and radiation therapy

Myasthenia gravis (MG) occurs in up to 44% of patients with thymoma. Thirty‐three percent of these neoplasms are invasive but extrathoracic disease is rare. Recently, we saw a patient with MG and recurrent, metastasizing mixed lymphoepithelial thymoma, whose disease was resistant to combination chemotherapy and radiotherapy but who responded dramatically to treatment with daily glucocorticoids. Thus, therapy with daily glucocorticoids should be considered in the treatment of invasive or metastatic thymoma associated with MG, including when conventional surgery, radiotherapy, and chemotherapy have failed.

Electrophysiologic endpoint measures in a multicenter ALS drug trial

We report the analysis of a battery of secondary electrophysiologic measurements to assess the progression of amyotrophic lateral sclerosis (ALS) in a two center, six month, double-blind, three arm trial comparing branched chain amino acids to L-threonine with pyridoxal 5-phosphate to placebo. The endpoint measurements were chosen to separately assess the effects of lower motor neuron loss and collateral reinnervation. For tests of inter-center reliability, we found no differences that could not be readily explained by variations in electrophysiologic testing techniques. Since the drug study was negative for the primary endpoint measure (muscle strength), we combined data from both centers and the three treatment arms. For measures of progression, all measures changed in the expected direction during the 6 months of the trial. We conclude that a battery of electrophysiologic measures can be used in a multicenter ALS drug trial to provide information on changes in lower motor neuron numbers and the effects of collateral reinnervation.

Benign autosomal dominant syndrome of neuronal Charcot‐Marie‐Tooth disease, ptosis, parkinsonism, and dementia

We present a kindred with a previously undescribed combination of neuronal Charcot-Marie-Tooth disease, ptosis, parkinsonism, and mild dementia. The propositus, a 72-year-old man, had pes cavus, peripheral neuropathy, ptosis, parkinsonism, hyperreflexia, orthostatic hypotension, central hypoventilation, and mild dementia. Peripheral electro-physiologic studies showed features of an axonal neuropathy. The electroencephalogram showed intermittent 2 to 4 Hz activity symmetrically in the hemispheres. Several family members in 3 generations had pes cavus, neuropathy, ptosis, parkinsonism, and dementia although not all of the features were consistently present. Survival past the 7th decade was common. Autopsy in 2 affected members revealed the neuropathy to be axonal in type and showed mild to moderate loss of anterior horn cells in the spinal cord and pigmentary loss with gliosis in the substantia nigra. This is a unique, benign, autosomal dominant syndrome which shows complete penetrance, variable expression, and both central and peripheral nervous system involvement.