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Patient: Male, 25 Final Diagnosis: Charcot-Marie-Tooth 1 Symptoms: Muscular • spasticity Medication: Oxandrolone Clinical Procedure: Neural and muscle biopsies Specialty: Neurology Objective: Unusual setting of medical care 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.

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 (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.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.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).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.

To look for an association between restless legs syndrome (RLS) and type 2 diabetes in a case-control study; to analyze the characteristics of RLS in diabetic patients; and to identify possible risk factors for the development of RLS in diabetic patients.A case-control study.Diabetic outpatient clinic of a major university hospital.One hundred twenty-four consecutive outpatients with diabetes and 87 consecutive controls with a previous diagnosis of other endocrine disease.RLS was diagnosed using the criteria of the International RLS Study Group, and severity of RLS was assessed using the International RLS Study Group Rating Scale. Characteristics of RLS and several laboratory parameters were investigated in diabetic patients and controls affected by the sleep disorder. A clinical diagnosis of polyneuropathy was assessed to evaluate its role as a risk factor for RLS in diabetic patients.RLS was diagnosed in 22 diabetic patients (17.7%) and in only 5 controls (5.5%), 3 of whom had pituitary and 2 had adrenal gland disorders, and RLS was independently associated with type 2 diabetes (P0.04). Even if a clinical diagnosis of polyneuropathy was made in only 27% of diabetic patients affected by RLS, after multivariate logistic regression, the presence of polyneuropathy was the only variable associated with RLS in diabetics (odds ratio, 7.88; 95% confidence interval, 1.34-46.28; P0.02). RLS in diabetics showed a frequency of positive family history lower than that known for primary RLS, showed a late age of onset, and manifested itself after the diagnosis of diabetes was made.This is the first controlled study confirming a significant association between RLS and type 2 diabetes. In diabetic patients, polyneuropathy represents the main risk factor for RLS. However, polyneuropathy only partially explains the increased prevalence of RLS in type 2 diabetics. Clinical characteristics of RLS in diabetic patients are those of a secondary form.

Background and objective: Cryoglobulinaemic neuropathy (CN) is probably common, as it is usually related to HCV infection. The aim of this study was to delineate the clinical spectrum of CN in a large series and to investigate the factors influencing its expression. Methods: Seventy one consecutive patients (12 men, 59 women), diagnosed as having CN on the basis of clinical features of neuropathy, clinical and serological findings of mixed cryoglobulinaemia, and exclusion criteria, were identified during a six year period. All patients underwent clinical examination, and electrophysiological and laboratory investigations. Results: Results of the patients with "pure" CN (n = 54) and those with comorbidities (n = 17) were evaluated separately. Of the former 76% had sensory neuropathy (including selective small fibre sensory neuropathy (SFSN) in 14 patients), 15% had sensorimotor polyneuropathy, and 9% had mononeuritis multiplex. The pattern of distribution was similar in the patients with comorbidities. In 30/54 patients, CN was the first manifestation of cryoglobulinaemia. Patients with mild cryoglobulinaemic syndrome had sensory neuropathy more frequently than patients with active syndrome (p

This report describes a 26 year old woman with a Coxsackie B virus infection complicated by an acute pandysautonomic and sensory neuropathy. Electrophysiological studies suggested an axonal neuropathy. A sural nerve biopsy performed early in the disease showed axonal degeneration with a virtual absence of unmyelinated fibres and moderate loss of myelinated fibres, mainly affecting the small fibres; this differs from previous reports. An immune-mediated or direct virus action might explain the pathogenesis of this unusual evolution of a viral infection.

Clinical and electrophysiological signs of peripheral neuropathy were found in 10 of 46 patients (21.7%) with primary Sjogren's syndrome, symmetric polyneuropathy in seven (mainly sensory in five, mainly autonomic in two), sensory neuronopathy in two patients, and mononeuropathy multiplex in one patient. Peripheral neuropathy was the presenting manifestation in five patients (10.9%). Onset of the disease after 50 years was significantly more common in the polyneuropathy group (six of seven) than in non-neuropathic patients with primary Sjogren's syndrome (14 of 36; p = 0.034). No other difference in clinical or laboratory variables between neuropathic and non-neuropathic patients with primary Sjogren's syndrome was found. Neurophysiological study showed variable findings predominantly suggesting an axonopathy. Nerve biopsy showed moderate remyelination and regeneration in four patients, and fibre loss, mainly of large size, in three. Necrotising vasculitis was not seen but alterations of the endoneurial microvessels were prominent.

We read with interest the description of a family with sensory inheritance. A form of HSAN characterized by late onset sensory ataxia was reported in another Dutch family (Staal ataxic neuropathy of autosomal dominant inheritance (van Dijk et al., 1995). Unfortunately, the Dutch authors omitted and Mechelse, 1978) which, however, showed a recessive mode of inheritance, whereas Robinson et al. (1977) described to discuss our report of a family with similar features which appeared in a Dutch journal (Marbini et al., 1994), classified an autosomal dominant form of HSAN with ataxia, but with onset usually in the first two decades. Additional features as hereditary sensory and autonomic neuropathy (HSAN) with ataxia and late onset. were represented by deafness in our family, and oculomotor disorder in the Dutch family. This probably reflects a The proband was a 66-year-old man who complained of unsteady gait, especially during walking in the dark, by age multisystem involvement, as other patients with HSAN and ataxia showed deafness (Robinson et al., 1977) or oculomotor 60 years. Neurological examination showed severe hearing loss, normal limb muscle bulk and strength, absent deep dysfunction (Staal and Mechelse, 1978). Sural nerve biopsy findings were similar in our case and in the Dutch patient, tendon reflexes in the ankles and marked sensory loss in the extremities, especially for the position sense, with severe showing severe loss of myelinated fibres, and moderate changes of the unmyelinated fibres. The most remarkable sensory ataxia. Investigations, including CT and MRI brain scans, were unremarkable except for sensorineural hearing difference was in the somatosensory evoked potentials, which were severely affected in three members of the Dutch family, loss and abnormal autonomic function tests. Neurophysiological study showed normal EMG, extremely reduced or but normal in our proband. This would point to involvement of dorsal root ganglia sensory neurons and distal involvement absent sensory action potentials (SAP), but only minor alterations in the motor nerves. Median and peroneal somatoin the peripheral nerves, respectively. It is also possible, however, that since the disease focuses on the peripheral sensory evoked potentials were normal. Sural nerve biopsy showed a severe loss of myelinated fibres of all calibres sensory neurons, as suggested by Dyck (1993), degeneration involves either the peripherally and centrally directed axons (622/mm2), whereas the unmyelinated fibre population was relatively less involved (7772/mm2; control 32000/mm2). of the dorsal root ganglion cells, or just the peripheral axons (Thomas, 1982). Biopsy of the peroneus brevis muscle showed normal findings. The patient’s brother, aged 62 years, who also complained In our opinion, these cases may represent a subset of autosomal dominant HSAN, or HSAN 1 described by Dyck of swaying for the last few years, showed marked sensory ataxia, absent Achilles tendon reflexes, and deficit in all (1993). This form is usually characterized by acrodystrophic symptoms with onset in the 2nd–3rd decade, but there is sensation modalities in the lower limbs, with normal EMG and electroneurography of the motor nerves, but extremely great variability in the onset and progression of the disease (Dyck, 1993). Our morphometric findings of profound loss of decreased amplitude or absence of the SAPs. Loss of balance with onset in the sixth decade was also myelinated fibres with a relative preservation of unmyelinated fibres do not fit with previous data on HSAN I by Dyck (loss reported in the father and in another brother, both deceased. Neurological examination was normal in the proband’s sons, of unmyelinated fibres and small myelinated fibres) and by Danon and Carpenter (1985) (uniform loss for every fibre aged 18–40 years, as were clinical and electrophysiological study and autonomic function tests in the 35-year-old type), but rather resemble the pathological features of HSAN II (Nukada et al., 1982). A minor involvement of the daughter of the patient’s 62-year-old brother. The paper of van Dijk et al. (1995), and ours, clearly unmyelinated nociceptive fibres could explain the absence of acrodystrophy, and this could result, in turn, in a delayed define a form of HSAN characterized clinically by sensory ataxia and late onset in the fifth or sixth decade, documented manifestation of the disease. Whether the differences between dominant HSN with ataxia and the classical form of HSAN in two generations, consistent with autosomal dominant

The prevalence of various forms of peripheral neuropathy has not been previously assessed in large series of patients with essential mixed cryoglobulinaemia (EMC). Clinical and electrophysiological signs of peripheral neuropathy were observed in 21 of 37 EMC patients, consisting of polyneuropathy in 19, mononeuropathy or multiple mononeuropathy in eight, and both in six. The various forms of peripheral neuropathy occurred differently in the subgroups of EMC. Isolated polyneuropathy was more common with type II (eight of 10) than type III EMC (two of eight). Multifocal neuropathy, in association with polyneuropathy, was the most common form in type III EMC (five of eight). Patients with peripheral neuropathy and type II EMC were significantly older than type II EMC patients without neuropathy, regarding present age and age of onset of EMC. Patients with peripheral neuropathy and type III EMC tended to have higher values of ESR and IgM than type III EMC patients without neuropathy. Electrophysiological findings and sural nerve biopsy specimens (nine cases) showed prominent axonal changes. Vascular changes included vasculitis and alterations of the endoneurial microvessels in type II and type III EMC. Our findings suggest that distinct pathogenic factors are implicated in the subgroups of cryoglobulinaemic neuropathy, possibly inducing different types of vascular changes underlying polyneuropathy or, respectively, mononeuropathy and multiple mononeuropathy.

We investigated the immunohistochemical distribution of cytoskeletal proteins in smooth muscles of 15 patients with Duchenne muscular dystrophy (DMD), 8 patients with Becker muscular dystrophy (BMD), 28 patients with various neuromuscular diseases, and 2 normal controls, performing skin and muscle biopsies. Dystrophin immunostaining confirmed absent reaction in the arrector pili muscles of DMD patients, faint positive reaction in BMD patients, and strong dystrophin reaction in patients with other neuromuscular diseases and normal controls. Immunostaining of utrophin was positive with variable intensity in the arrector pili muscles in all DMD patients. In BMD patients, utrophin was faintly expressed in the arrector pili muscles in 2 cases, and negative in the other 5 patients. In the other cases of neuromuscular diseases and in normal controls, immunostaining for utrophin was negative in the arrector pili muscles. Staining of the capillary endothelial cells and muscular vessel walls was seen in normal controls, as well as in DMD, BMD, and other neuromuscular diseases. Vinculin, vimentin and desmin were expressed both in arrector pili smooth muscles and in vessel walls of patients with dystrophinopathy and other neuromuscular diseases, as well as in normal controls. Thus utrophin is normally expressed in the smooth muscle of the vessels and its expression does not vary in neuromuscular diseases. On the contrary, in the arrector pili smooth muscle utrophin is not expressed in normal controls but it is in dystrophinopathies, paralleling the findings in striated muscle, which expresses utrophin in a reciprocal manner with respect to dystrophin.

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.