André Truffert

Epilepsy and cerebellar ataxia associated with anti-glutamic acid decarboxylase antibodies

Anti-glutamic acid decarboxylase (GAD) antibodies are described in stiff-person syndrome and also in other neurological syndromes, including cerebellar ataxia and epilepsy. This paper reports the case of a patient who had chronic focal epilepsy, upbeat nystagmus and cerebellar ataxia, associated with a polyautoimmune response including anti-GAD antibodies. Both gait and nystagmus improved markedly after immunosuppressive treatment with corticosteroids and azathioprine. After the introduction of benzodiazepines, previously refractory seizures were completely controlled. Anti-GAD antibodies should be actively sought out in pharmacoresistant epilepsy, particularly if other neurological abnormalities are present. Combined treatment with immunosuppressants and γhydroxybutyric acidergic agents may be highly effective.

Ryanodine receptor fragmentation and sarcoplasmic reticulum Ca2+ leak after one session of high-intensity interval exercise

Significance High-intensity interval training (HIIT) has become popular because it is a time-efficient way to increase endurance. An intriguing and so-far-unanswered question is how a few minutes of HIIT can be that effective. We exposed recreationally active men to one session of three to six sets of 30-s high-intensity cycling exercise. Muscle biopsies taken 24 h later showed an extensive fragmentation of the sarcoplasmic reticulum (SR) Ca2+ channels, the ryanodine receptor 1 (RyR1). In isolated mouse muscle fibers, this fragmentation was accompanied by increased SR Ca2+ leak, which can trigger mitochondrial biogenesis. The HIIT-induced RyR1 fragmentation did not occur in muscles exposed to antioxidant, which offers an explanation for why antioxidants blunt effects of endurance training. High-intensity interval training (HIIT) is a time-efficient way of improving physical performance in healthy subjects and in patients with common chronic diseases, but less so in elite endurance athletes. The mechanisms underlying the effectiveness of HIIT are uncertain. Here, recreationally active human subjects performed highly demanding HIIT consisting of 30-s bouts of all-out cycling with 4-min rest in between bouts (≤3 min total exercise time). Skeletal muscle biopsies taken 24 h after the HIIT exercise showed an extensive fragmentation of the sarcoplasmic reticulum (SR) Ca2+ release channel, the ryanodine receptor type 1 (RyR1). The HIIT exercise also caused a prolonged force depression and triggered major changes in the expression of genes related to endurance exercise. Subsequent experiments on elite endurance athletes performing the same HIIT exercise showed no RyR1 fragmentation or prolonged changes in the expression of endurance-related genes. Finally, mechanistic experiments performed on isolated mouse muscles exposed to HIIT-mimicking stimulation showed reactive oxygen/nitrogen species (ROS)-dependent RyR1 fragmentation, calpain activation, increased SR Ca2+ leak at rest, and depressed force production due to impaired SR Ca2+ release upon stimulation. In conclusion, HIIT exercise induces a ROS-dependent RyR1 fragmentation in muscles of recreationally active subjects, and the resulting changes in muscle fiber Ca2+-handling trigger muscular adaptations. However, the same HIIT exercise does not cause RyR1 fragmentation in muscles of elite endurance athletes, which may explain why HIIT is less effective in this group.

Amyotrophic lateral sclerosis versus cervical spondylotic myelopathy: a study using transcranial magnetic stimulation with recordings from the trapezius and limb muscles

OBJECTIVE We report an electrophysiological method to differentiate amyotrophic lateral sclerosis (ALS) from cervical spondylotic myelopathy (CSM). METHODS Motor evoked potentials (MEPs) by transcranial magnetic stimulation were investigated in patients with ALS (n=10) and CSM (n=9). In addition to limb MEPs using the triple stimulation technique (TST) at upper limbs, MEPs recorded from trapezius muscles were compared with those obtained from 23 normal subjects. The parameters studied were: central motor conduction time, amplitude ratio and, for the trapezius, the interside asymmetry. RESULTS Whereas limb MEPs were abnormal in most ALS and CSM patients (17/19), trapezius MEPs were abnormal in all ALS patients, and normal in 8 out of 9 CSM patients. CONCLUSION Recording of trapezius MEPs is a valuable addition to the limb MEPs study, since it distinguishes ALS from SCM in most patients.

Peripheral Autoimmune Neuropathy Assessed Using Corneal In Vivo Confocal Microscopy

BACKGROUND Corneal nerves can be examined using in vivo confocal microscopy (IVCM). This new technique permits sequential observation of the corneal subbasal nerve plexus and detects early signs of diabetic peripheral neuropathy. OBJECTIVE To describe a patient with autoimmune peripheral neuropathy followed up using corneal IVCM. DESIGN Case report. SETTING Clinic of neurology, Geneva, Switzerland. Patient A 56-year-old man with peripheral neuropathy diagnosed as anti-myelin-associated glycoprotein neuropathy. His symptoms initially worsened despite the administration of intravenous immunoglobulins and plasma exchange. Evolution was eventually favorable after rituximab and corticosteroids were given. At 1-year follow-up, clinical recovery was almost complete, and the patient was stable according to the results of clinical and electrophysiologic assessments. Main Outcome Measure Corneal nerve measurement by IVCM. RESULTS Examination of corneal nerves using IVCM at 2 different times during the patients clinical evolution (peak disease and recovery phase) demonstrated histologic signs that correlated with the results of clinical and electrophysiologic assessments. CONCLUSION This observation supports the hypothesis that corneal IVCM could also be helpful for the early detection or follow-up of autoimmune peripheral neuropathy.

Cutaneous silent period in carpal tunnel syndrome

The cutaneous silent period (CuSP), a transient suppression of electromyographic activity that follows painful stimuli, allows an indirect study of the small‐diameter A‐δ fibers. To assess the function of these fibers in peripheral nerve disorders, we compared the CuSP of 40 controls to that of 40 patients with carpal tunnel syndrome (CTS) and one patient with a traumatic transection of the median nerve. Patients with CTS were divided into three severity groups, based on electrophysiological data. In CTS, digit 2 evoked CuSP onset latency was increased in all groups, and CuSP duration from abductor digiti minimi was reduced in all groups. In our series, although some parameters of the CuSP were altered, only transection of the nerve abolished it. A‐δ fibers are robust, probably due to their less vulnerable small diameter. This characteristic may be useful to study various conditions and essential for patients to retain some sensation within the median nerve territory. Muscle Nerve, 2006

RELAPSING RHABDOMYOLYSIS DUE TO PEROXISOMAL α-METHYLACYL-COA RACEMASE DEFICIENCY

A right-handed man born of nonconsanguineous parents had schizophrenia from age 23 with recurrent bouts of neuroleptic malignant syndrome with rhabdomyolysis. These episodes were associated with myalgia, muscle weakness, and high creatinine kinase (CK) levels, up to 58,000 U/L (normal 47–222 U/L). Rhabdomyolysis also occurred with flu-like infections, twice, with CK levels at 42,000 U/L and 141,000 U/L respectively and one asymptomatic episode occurred after general anesthesia (CK 73,000 U/L). The paternal grandmother had schizophrenia. In 2007, at age 33, the patient developed fever and headache, followed by right sensorimotor deficit, aphasia, right hemianopsia, and complex partial seizures, with spontaneous recovery after several weeks. One year later, he had another febrile stroke-like episode with confusional state, left hemiparesis, and hemineglect syndrome. The first cerebral MRI, at age 23, showed T2-weighted increased signal in both thalami, the pons, and cerebral peduncles (figure, A). After the first stroke-like episode (in 2007), brain MRI showed edema involving the entire hemicortex of the left cerebral hemisphere, except for the mesiotemporal regions. Spectroscopy showed a nonspecific lactate peak and decreased NAA/choline ratio in the left parietal cortex. After the second event (in 2008), MRI showed new cortical edema …

Rapid cortical motor output map changes assessed by the triple stimulation technique

The amplitudes of motor evoked potentials (MEPs) were mapped by transcranial magnetic stimulation (TMS) using the triple stimulation technique (TST) in 11 normal individuals. Stimuli were given while the subjects were (a) distracted, (b) concentrating on their target (recorded) hand, and (c) concentrating on their contralateral hand. Within seconds, the proportion of excited motor units increased, similarly in all subjects, by an average of 70% from (a) to (b), and by 48% from (a) to (c). At the optimal stimulation site, results obtained with the TST were compared to those of conventional MEPs. The TST proved superior in detecting the rapid changes of the motor output caused by the non-specific mental tasks studied.

Corneal Nerves Alterations in Various Types of Systemic Polyneuropathy, Identified by In Vivo Confocal Microscopy

BACKGROUND In vivo confocal microscopy (IVCM) is a newly developed application to assess corneal nerve morphology. The purpose of the study is to evaluate the role of IVCM in the assessment of various types of polyneuropathy, and to define alterations of corneal nerves in such conditions. PATIENTS AND METHODS Eighteen patients with various types of polyneuropathy were characterized by clinical neurological and ophthalmic examinations, as well as by electroneuromyography (ENMG). Full thickness IVCM of corneal nerves was carried out on all patients and 15 age-matched eyes using Heidelberg Retina Tomograph II (HRT II). The subbasal nerve plexus were statistically analysed regarding long nerve fiber density, nerve branch density, nerve thickness, nerve bead number and nerve tortuosity. RESULTS In subbasal nerve plexus, the following three parameters were significantly reduced in patients with polyneuropathy compared to controls: long nerve fibre density (p < 0.01), nerve branch density (p < 0.001), and nerve bead number (p = 0.001). In addition, the average grade of nerve tortuosity was 2.87 +/- 0.97 in the polyneuropathic group and 1.17 +/- 0.68 in the control group (p < 0.0001). CONCLUSIONS IVCM allows a non-invasive, in vivo study of corneal nerves with high resolution. It therefore appears invaluable in clinical investigations. IVCM appears to be valuable in a large variety of polyneuropathic conditions.

Myasthenia gravis associated with HTLV‐I infection and atypical brain lesions

We report a patient who experienced progressive diplopia and distal weakness of the upper limbs. Magnetic resonance imaging of the brain showed extensive white matter lesions and analysis of cerebrospinal fluid revealed acute human T‐lymphotropic virus type I (HTLV‐I) infection. Myasthenia gravis (MG) was evidenced by electromyography (EMG) and antibodies against acetylcholine receptor. This unusual case of MG associated with HTLV‐I infection and brain‐restricted lesions underscores the possible link between viruses and MG pathogenesis. Muscle Nerve, 2006

Anti-TNF alpha medications and neuropathy.

We studied the clinical, electrophysiological, and pathological features, outcome, and frequency of anti‐tumor necrosis factor alpha (a‐TNF) medications‐induced neuropathies (ATIN) in patients with inflammatory disorders. Of 2,017 patients treated with a‐TNF medication, 12 patients met our inclusion criteria for a prevalence of 0.60% and an incidence of 0.4 cases per 1,000 person‐years. The median time from a‐TNF medication treatment to ATIN was 16.8 months (range 2–60 months). Six patients had focal or multifocal peripheral neuropathies. The other six had generalized neuropathies. For all, a‐TNF medication was stopped. Seven patients received immunoglobulin infusions. ATIN outcome was favorable in all but one patient. ATINs are rare and heterogeneous neuropathies. In 10 patients, the neuropathy was “inflammatory”, suggesting that it could be due to systemic pro‐inflammatory effects of a‐TNF agents.