Neuroregenerative Effect of Oxandrolone: A Case Report.

BACKGROUND: Anabolic steroids have the clinical effect of increasing protein synthesis in muscle and other tissues. The brain and spinal cord neurons have gonadal steroid receptors and various studies have shown at structural and molecular levels that androgenic steroids have a significant trophic effect on the brain and spinal cord. CASE REPORT: We evaluated the effect of Oxandrolone (an FDA-approved anabolic steroid) at the dose of 20 mg/day for 3 months added to concomitant exercise strength training 3 times a week in a patient affected by a demyelinating disease, Charcot-Marie-Toot 1 (CMT1). After the treatment, an increase in muscular strength and walking capacity was observed. Muscle biopsy revealed a significant increase of type grouping of muscle fibers, an expression of regeneration and reinnervation processes. CONCLUSIONS: Data ensuing from this single case-report suggest that anabolic androgenic steroids have a potential neuroregenerative effect, with an inherent improvement in neuromuscular efficiency through an increased myelin synthesis at peripheral nervous system site.

Non-length dependent small fiber neuropathy. a prospective case series.

We report the features of non-length dependent small fiber neuropathy (SFN) and compare them to those with distal length-dependent SFN. In a series of 224 consecutive neuropathy patients, we evaluated 44 patients with SFN diagnosed in the presence of both symptoms and signs. Eleven were classified as non-length dependent SFN. Disease associations were Sjögren's syndrome (two patients), impaired glucose tolerance, rheumatoid arthritis, hepatitis C virus, Crohn's disease, and idiopathic (five patients). In the 33 patients with distal SFN, the age of onset was significantly older and more had impaired glucose metabolism (16/33). In both groups, pain was mainly characterized as burning, but patients with non-length dependent SFN more often reported an "itchy" quality and allodynia to light touch.

Restless legs syndrome and painful neuropathy-retrospective study. A role for nociceptive deafferentation?

OBJECTIVES: Restless legs syndrome (RLS) occurs in polyneuropathy with small fiber involvement, possibly as a peculiar form of neuropathic pain; however, the relationship between pain and RLS has been poorly investigated in polyneuropathy. DESIGN, SETTING, AND PATIENTS: We evaluated retrospectively the occurrence of RLS in 102 consecutive patients with polyneuropathy manifesting with neuropathic pain or dysesthesia, referred to the Neuromuscular Center, using the National Institutes of Health criteria for RLS. The patients were classified in subgroups characterized respectively by allodynia (hyperphenomena), with reported unpleasant sensations evoked by tactile stimuli, and hypoalgesia (hypophenomena), with absent pain sensation to pinprick, according to putative mechanisms of pain. RESULTS: RLS was present in 41/102 patients (40.2%). It was significantly more frequent in the "hypoalgesia" (23/37) than in the "allodynia" subgroup (9/31; P = 0.008) and in the not classifiable cases (9/34; P = 0.004). CONCLUSIONS: RLS is frequent in painful polyneuropathy and is significantly associated with decreased small fiber input, thus nociceptive deafferentation may represent a factor interacting with RLS "generators," possibly at spinal level. We suggest that overactivity of the spinal structures implicated in RLS may be triggered by nociceptive deafferentation in a subgroup of patients with painful polyneuropathy. Our findings, prompting a mechanistic characterization of RLS associated with painful polyneuropathy, have to be confirmed in a prospective study.

Restless legs syndrome in diabetic neuropathy: a frequent manifestation of small fiber neuropathy.

As the occurrence of restless legs syndrome (RLS) in diabetes is controversial, the aim of this study was to assess the prevalence of RLS in a cohort of patients with diabetic neuropathy and to analyze the features of the associated neuropathy. We investigated the occurrence of RLS diagnosed in accordance with the criteria of the International Restless Legs Syndrome Study Group in a cohort of patients with polyneuropathy and mononeuropathy multiplex associated with diabetes mellitus (DM), or impaired glucose tolerance (IGT), or impaired fasting glucose (IFG) in a retrospective study. RLS was present in 33/99 patients with neuropathy associated with DM/IGT/IFG (84 with distal polyneuropathy and 15 with multiple mononeuropathy). Comparing patients with or without RLS, small fiber sensory neuropathy was more common in the RLS patients (15/33 vs. 15/66), as were symptoms of burning feet (10/33 vs. 6/66). In several patients, RLS was responsive to neuropathic pain medications. The frequent occurrence of RLS in association with thermal dysesthesias may reflect the involvement of small sensory fibers in the form of hyperexcitable C fibers or A-delta fiber deafferentation. We suggest that RLS may be triggered by abnormal sensory inputs from small fibers, especially involved in neuropathy associated with DM/IGT/IFG. Our data show that RLS is a relevant feature of diabetic neuropathy, as a frequent and potentially treatable manifestation of small fiber involvement in the course of DM and IGT/IFG.

Restless legs syndrome and polyneuropathy.

Restless legs syndrome (RLS), diagnosed according to the International RLS Study Group criteria, was investigated in 97 consecutive patients with polyneuropathy and found in 29 patients. RLS patients were more often women (22 of 29 vs. 33 of 68; P = 0.015), mainly with sensory neuropathy of small fiber type (15 of 29 vs. 16 of 68; P = 0.009). Changes of sensory action potentials were significantly less severe in RLS patients. In the RLS group, acquired neuropathies, and in particular dysimmune neuropathies, were significantly more frequent (27/29 vs. 46/68; P = 0.009). Thus, RLS is frequent in acquired polyneuropathy of sensory type and mild entity, mainly in women.

Sensory manifestations in Charcot-Marie-Tooth disease.

Involvement of sensory nerves in Charcot-Marie-Tooth (CMT) disease is well known, however, sensory symptoms are usually overlooked. To assess the frequency and features of sensory symptoms in a cohort of patients with CMT, we investigated in a prospective study 52 consecutive CMT patients, diagnosed on the basis of clinical, neurophysiological, and genetic features and classified in CMT type 1 (CMT1) (20 patients, including 14 with CMT1A) and CMT type 2 (CMT2) (32 patients). Positive sensory symptoms were reported by 28 patients (54%), including neuropathic pain in 6 patients. Pain, either neuropathic or nociceptive, was present in 29 patients (56%) and in 15 patients as a main symptom. Positive sensory symptoms were present in 24 of 32 CMT2 patients (75%) and in 4 of 20 CMT1 patients (20%) (p < 0.001); there was a presenting manifestation in 11/32 CMT2 patients vs. 1/20 in CMT1 patients (p = 0.018), and one of the main features in 6/32 CMT2 patients vs. 1/20 CMT1 patients. Frequency of positive sensory symptoms in CMT1A patients was similar to that of the entire CMT1 group. Within the CMT2 group, patients with positive sensory symptoms as a main or onset feature (11 patients) had significantly later onset (median 57 vs. 25 years; p = 0.042) and less severely impaired motor action potentials than CMT2 patients without positive sensory symptoms (8 patients). Nociceptive pain was especially frequent in CMT1A patients (10/14, 71%). Sensory manifestations in CMT seem more frequent than previously thought, especially in CMT2; however, their frequency may be different in the genetic subtypes of the disease and/or an expression of phenotypic variability. Sensory symptoms, and in particular pain, may represent an important issue in the management of CMT patients, especially in a physical medicine approach.

Cryoglobulinemia is a frequent cause of peripheral neuropathy in undiagnosed referral patients.

Cryoglobulinemia represents an emerging cause of peripheral neuropathy, especially in Southern Europe, in view of its relationship with hepatitis C virus infection. In a series of 100 consecutive referral patients with uncharacterized peripheral neuropathies, we systematically investigated cryoglobulinemia to assess its diagnostic yield. The most frequent diagnosis was hereditary neuropathy (33%), 29% were acquired neuropathies of different types, and no cause could be identified in 27%. Cryoglobulinemic neuropathy was diagnosed in 11 patients (7 women and 4 men), aged 54-77 (mean = 63.5 years), most presenting with sensory polyneuropathy, often asymmetrical. Cryoglobulin was also detected in 2 additional patients in whom a final diagnosis of non-Hodgkin lymphoma was made. Purpura was absent in 4 patients (and in 2 with lymphoma), or restricted to discrete manifestations in the remaining patients, which did not provide a clue to the diagnosis. Thus, search for cryoglobulin proves useful in a substantial number of undiagnosed peripheral neuropathies (11% to 13% in our series), even in the absence of typical skin lesions, and it is recommended as a first-line investigation in patients with unexplained neuropathy presenting in middle to older age.

Immunohistochemical study of muscle biopsy in children with cerebral palsy.

Muscle biopsy was examined in 20 children with cerebral palsy, using immunohistochemical methods for marker of denervation neural cell adhesion molecules (N-CAM) in addition to standard techniques. Histological and histochemical study showed mild myopathic changes, type 1 predominance, and type 1 and type 2 hypotrophy, in accord with previous observations. Immunohistochemical study showed N-CAM expression in most biopsies (15/20), usually in scattered fibers, whereas in four patients aged less than 6 years it was expressed in grouped fibers. Our study supports the hypothesis of motor unit remodeling as a consequence of spasticity, especially in early phases of the disease.